Craig


Email

441E Biochemistry Laboratories
433 Babcock Drive
Madison, WI 53706-1544
USA

(608) 263-7105

   

Elizabeth A Craig

           

Elizabeth Cavert Miller Professor, Steenbock Professor of Microbial Science,
Chair, Department of Biochemistry
B.S., University of Rhode Island;
Ph.D., Washington University School of Medicine

      

Folding and remodeling of proteins in the cell - the function of molecular chaperones

Proteins are dynamic macromolecules. In all living cells molecular chaperones play critical roles in remodeling protein structure -- assisting de novo protein folding, preventing protein aggregation, facilitating assembly and disassembling of protein complexes and modulating protein:protein interactions.

Our goals are two-fold, to understand the basis of: (1) the mechanism of action of molecular chaperones in specific complex biological processes such as translocation of proteins across membranes and the prion propagation and (2) functional differences amongst molecular chaperones that allows them to assist in a multiplicity of physiological processes.

Hsp70 and J-protein Families: Generalists and Specialists
Complementary to our studies of molecular chaperones in particular cellular processes (described below) we aim to understand the basis of functional differences amongst molecular chaperones. Unlike many molecular chaperones, Hsp70s-based chaperone machines are encoded by sizeable multigene families. We focus on the J-protein component of Hsp70-based machinery, as J-protein partners orchestrates the ability of Hsp70 to participate in a wide array of complex and diverse biological processes.

Propagation of prions via action of molecular chaperones
Proteins can exist in more than one conformation. Particular proteins, called prions, can acquire conformations that are self-propagating. Yeast contains several prions whose conformation is profoundly affected by molecular chaperones. In each case, particular chaperones, a J-protein/Hsp70 pair and a AAA+ ATPase are absolutely required for maintenance of the prion form within a population of cells. Our goal is to understand the mechanism by which these chaperones affect self-replicating forms of proteins.

Translocation of proteins across mitochondrial membranes driven by a chaperone-based “import motor”
The vast majority of the hundreds of proteins of the mitochondrial matrix are synthesized on cytosolic ribosomes. Thus, efficient import of proteins is critical for mitochondrial function. The import motor required for driving proteins across the inner membrane into the matrix is composed of 5 essential components, with the matrix Hsp70 molecular chaperone, at its core. Our goal is to dissect the specialized regulated protein:protein interactions amongst the components and the translocon channel that have evolved to drive efficient translocation of polypeptides across the membrane.

Specialized ribosome-associated molecular chaperones
During their synthesis on ribosomes, proteins are particularly susceptible to aggregation, which prohibits their proper folding. We are studying ribosome-associated molecular chaperones that are tethered near the site from which the nascent chain exits the ribosome tunnel. Our goal is to determine how this chaperone and associated factors aid in folding of newly synthesized proteins.

Conserved system for assembly of Fe/S clusters and their insertion into proteins
Mitochondria contain a complex system for assembly of Fe/S metal centers and their insertion into proteins. A specialized J-protein/ Hsp70 molecular chaperone pair is a critical part of this system, interacting specifically with the scaffold protein on which clusters are first built and facilitating cluster transfer. We aim to unravel the mechanism of action of this dedicated chaperone system and the regulation of expression of its components.

For more information see the Craig Lab Website



    

 

 

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